The objective of this proposal is to clarify the nature of the immune system and the skin in a variety of benign and malignant conditions. The methodology of contemporary cellular immunology will be utilized in studies in mice to further our understanding of the pathogenesis and immunobiology of benign (allergic contact dermatitis or ACD) and malignant (e.g., mycosis fungoides) skin diseases. Both of these conditions are characterized by the presence of prominent lymphoid cell (normal and/or typical) infiltrates not only in the dermis, but also in the epidermis. Analysis of the available clinical and experimental data has suggested several testable hypotheses, including the possibility that epidermal invasion is a property of a subpopulation of T cells. The proposed studies of adoptive transfer of ACD reactions in mice are designed to systematically characterize (by physical properties and cell surface marker analysis) both the immunologically specific cells which are responsible for initiating those reactions and the cells which are nonspecifically recruited into ACD reaction sites. The specific initiator cells produced under varying conditions of immunization, and enriched by such techniques as adsorption or antigen-coated cell monolayers, will be analyzed for their phenotype and their localization pattern within the reaction site (determined by autoradiography). The relative abilities of discrete cells within the skin (e.g., Langerhans cells vs. keratinocytes) to serve as specific targets of immune recognition in ACD reactions will be analyzed, as will the roles of defined subregions of the major histocompatability complex on antigen-presenting cells in the triggering of ACD reactive cells. The relative abilities of variously fractionated subpopulations of normal and malignant lymphoid cells to be nonspecifically recruited into ACD sites will be quantitatively compared by radiolabeling those subpopulations with either 51Cr or 3H-uridine, the latter procedure allowing, by autoradiography, determination of the precise sites of localization (e.g., dermis vs. epidermis) of the injected cells. Finally, these same phenotypically-characterized mouse lymphomas will be analyzed for their intracutaneous growth pattern as an initial step toward development of an animal model for the human cutaneous lymphomas.